Allergic sensitivity to natural rubber latex has become a major occupational hazard of healthcare workers and some patients with frequent latex rubber exposures. Between 2.2 and 10.7% of healthcare workers and up to 50% of children with spina bifida are at risk for systemic reactions to rubber products, mainly latex gloves. Since complete avoidance is difficult in most medical environments, latex allergy can necessitate involuntary career changes with substantial economic and emotional consequences. Using a latex allergen extract now under FDA review as a proposed diagnostic reagent, this project will continue development of a natural exposure model of respiratory latex allergy in clinical studies to demonstrate the safety and efficacy of immunotherapy for IgE-dependent latex allergy. The specific aims are: (1) to complete a Phase I clinical trial of immunotherapy with a candidate extract of non-ammoniated latex. This study is currently in progress with three of six latex-allergic healthcare workers enrolled. Safety, IgG and IgE antibody responses) and evidence of desensitization (skin test titrations) are being studied. (2) to determine in a randomized, placebo-controlled clinical trial the safety and clinical efficacy of immunotherapy in patients with l disabling occupational allergy to latex proteins. Subjects will be health professionals with clinically significant respiratory or anaphylactic reactions to latex and documented failure of attempts at avoidance. The primary endpoint will be sensitivity to latex as determined by the hooded chamber graded exposure technique. Secondary endpoints for the clinical trial will include immunologic changes (IgG and IgE fluxes), skin test sensitivity, adverse reaction rates, and where possible assessment of work-related symptoms. In parallel we propose (3) to prospectively evaluate cohorts of new nursing students and children with spina bifida in order to determine the initial prevalence rates, the rate of new sensitization over a five-year period, and the risk factors related to the development of sensitivity. Enrolled cohorts will be followed annually to assess latex exposure, clinical reactivity, and skin test reactivity. The purpose is to evaluate clinical effectiveness of latex avoidance policies currently in use. The long-term objective of this research plan is to develop a useful therapeutic alternative for latex sensitive healthcare workers and selected patients who have failed avoidance, and to document prospectively the effectiveness of current latex containment policies on the incidence of new sensitization. Potential benefits of successful immunotherapy include a reduction in professional disability, prevention of chronic disease, expanded occupational choices and increased work productivity for those affected. Knowledge of the effectiveness of containment practices will help shape future occupational health polices.